Computational tool for the early screening of monoclonal antibodies for their viscosities

TLDR

Highly concentrated antibody solutions frequently have high viscosities that hinder development, manufacturing, and administration, and because the antibody sequence determines viscosity, a sequence‑ or structure‑based tool to identify high‑viscosity antibodies is essential for early development. The authors introduce a spatial charge map (SCM) tool to identify highly viscous antibodies directly from their sequence. SCM achieves this by using homology modeling to generate the antibody’s 3‑dimensional structure and map spatial charge. Validated across three organizations, SCM accurately identifies high‑viscosity antibodies and supports high‑throughput automated screening for low‑viscosity candidates.

Abstract

Highly concentrated antibody solutions often exhibit high viscosities, which present a number of challenges for antibody-drug development, manufacturing and administration. The antibody sequence is a key determinant for high viscosity of highly concentrated solutions; therefore, a sequence- or structure-based tool that can identify highly viscous antibodies from their sequence would be effective in ensuring that only antibodies with low viscosity progress to the development phase. Here, we present a spatial charge map (SCM) tool that can accurately identify highly viscous antibodies from their sequence alone (using homology modeling to determine the 3-dimensional structures). The SCM tool has been extensively validated at 3 different organizations, and has proved successful in correctly identifying highly viscous antibodies. As a quantitative tool, SCM is amenable to high-throughput automated analysis, and can be effectively implemented during the antibody screening or engineering phase for the selection of low-viscosity antibodies.